Transcriptome analysis of glioma cells for the dynamic response to gamma-irradiation and dual regulation of apoptosis genes: a new insight into radiotherapy for glioblastomas

doi:10.1038/cddis.2013.412

	Transcriptome analysis of glioma cells for the dynamic response to gamma-irradiation and dual regulation of apoptosis genes: a new insight into radiotherapy for glioblastomas
	Ma, H.; Rao, L.; Wang, H. L.; Mao, Z. W.; Lei, R. H.; Yang, Z. Y.; Qing, H.; Deng, Y. L.
	2013
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	4
摘要	Ionizing radiation (IR) is of clinical importance for glioblastoma therapy; however, the recurrence of glioma characterized by radiation resistance remains a therapeutic challenge. Research on irradiation-induced transcription in glioblastomas can contribute to the understanding of radioresistance mechanisms. In this study, by using the total mRNA sequencing (RNA-seq) analysis, we assayed the global gene expression in a human glioma cell line U251 MG at various time points after exposure to a growth arrest dose of gamma-rays. We identified 1656 genes with obvious changes at the transcriptional level in response to irradiation, and these genes were dynamically enriched in various biological processes or pathways, including cell cycle arrest, DNA replication, DNA repair and apoptosis. Interestingly, the results showed that cell death was not induced even many proapoptotic molecules, including death receptor 5 (DR5) and caspases were activated after radiation. The RNA-seq data analysis further revealed that both proapoptosis and antiapoptosis genes were affected by irradiation. Namely, most proapoptosis genes were early continually responsive, whereas antiapoptosis genes were responsive at later stages. Moreover, HMGB1, HMGB2 and TOP2A involved in the positive regulation of DNA fragmentation during apoptosis showed early continual downregulation due to irradiation. Furthermore, targeting of the TRAIL/DR5 pathway after irradiation led to significant apoptotic cell death, accompanied by the recovered gene expression of HMGB1, HMGB2 and TOP2A. Taken together, these results revealed that inactivation of proapoptotic signaling molecules in the nucleus and late activation of antiapoptotic genes may contribute to the radioresistance of gliomas. Overall, this study provided novel insights into not only the underlying mechanisms of radioresistance in glioblastomas but also the screening of multiple targets for radiotherapy.
关键词	Transcriptome gamma-irradiation apoptosis dynamic response glioblastoma radioresistance
学科领域	Cell Biology
DOI	10.1038/cddis.2013.412
收录类别	SCI
语种	英语
WOS关键词	DNA-DAMAGE ; IN-VITRO ; IONIZING-RADIATION ; CANCER-CELLS ; EXPRESSION ; CYCLE ; P53 ; RADIOSENSITIZATION ; ACTIVATION ; INHIBITION
WOS研究方向	Science Citation Index Expanded (SCI-EXPANDED)
WOS记录号	WOS:000326967100081
出版者	NATURE PUBLISHING GROUP
文献子类	Article
出版地	LONDON
资助机构	Ministry of Science and Technology, China(Ministry of Science and Technology, China) ; National Natural Science Foundation of China(National Natural Science Foundation of China (NSFC)) ; opening foundation of the State Key Laboratory of Space Medicine Fundamentals and Application, Chinese Astronaut Research and Training Center
作品OA属性	Green Published, gold
引用统计	被引频次：31[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ibcas.ac.cn/handle/2S10CLM1/27784
专题	中科院植物分子生理学重点实验室
作者单位	1.[Ma, H. 2.Rao, L. 3.Wang, H. L. 4.Lei, R. H. 5.Yang, Z. Y. 6.Qing, H. 7.Deng, Y. L.] Beijing Inst Technol, Sch Life Sci, Beijing 100081, Peoples R China 8.[Mao, Z. W.] Chinese Acad Sci, Inst Bot, Key Lab Plant Mol Physiol, Beijing 100093, Peoples R China
推荐引用方式 GB/T 7714	Ma, H.,Rao, L.,Wang, H. L.,et al. Transcriptome analysis of glioma cells for the dynamic response to gamma-irradiation and dual regulation of apoptosis genes: a new insight into radiotherapy for glioblastomas[J]. CELL DEATH & DISEASE,2013,4.
APA	Ma, H..,Rao, L..,Wang, H. L..,Mao, Z. W..,Lei, R. H..,...&Deng, Y. L..(2013).Transcriptome analysis of glioma cells for the dynamic response to gamma-irradiation and dual regulation of apoptosis genes: a new insight into radiotherapy for glioblastomas.CELL DEATH & DISEASE,4.
MLA	Ma, H.,et al."Transcriptome analysis of glioma cells for the dynamic response to gamma-irradiation and dual regulation of apoptosis genes: a new insight into radiotherapy for glioblastomas".CELL DEATH & DISEASE 4(2013).

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